Method of maintaining constant arterial PCO2 and measurement of anatomic and alveolar dead space

ABSTRACT

A method to maintain isocapnia for a subject. A fresh gas is provided to the subject when the subject breathes at a rate less than or equal to the fresh gas flowing to the subject. The fresh gas flow equal to a baseline minute ventilation minus a dead space gas ventilation of the subject contains a physiological insignificant amount of CO 2 . An additional reserve gas is provided to the subject when the subject breathes at a rate more than the fresh gas flowing to the subject. The reserve gas has a partial pressure of carbon dioxide equal to an arterial partial pressure of carbon dioxide of the subject. A breathing circuit is applied to the method to maintain isocapnia for a subject. The breathing circuit has an exit port, a non-rebreathing valve, a source of fresh gas, a fresh gas reservoir and a reserve gas supply.

RELATED APPLICATIONS

The present application is a continuation of U.S. application Ser. No.10/135,655 entitled “METHOD OF MAINTAINING CONSTANT ATERIAL PCO₂ ANDMEASUREMENT OF ANATOMIC AND ALVEOLAR DEAD SPACE” filed Apr. 30, 2002,now U.S. Pat. No. 6,799,570 which is a continuation-in-part ofapplication Ser. No. 09/676,899, filed on Oct. 2, 2000.

STATEMENT RE FEDERALLY SPONSORED RESEARCH/DEVELOPMENT

(Not applicable)

BACKGROUND OF INVENTION

The present invention relates to a method to maintain isocapnia whenbreathing exceeds baseline breathing and a circuit therefor. Preferably,the circuit includes a non-rebreathing valve, a source of fresh gas, afresh gas reservoir and a source of gas to be inhaled when minuteventilation exceeds fresh gas flow. Preferably the flow of the fresh gasis equal to minute ventilation minus anatomic dead space. Any additionalinhaled gas exceeding fresh gas flow has a partial pressure of CO₂ equalto the partial pressure of CO₂ of arterial blood.

Venous blood returns to the heart from the muscles and organs partiallydepleted of oxygen (O₂) and a full complement of carbon dioxide (CO₂).Blood from various parts of the body is mixed in the heart (mixed venousblood) and pumped into the lungs via the pulmonary artery. In the lungs,the blood vessels break up into a net of small vessels surrounding tinylung sacs (alveoli). The vessels surrounding the alveoli provide a largesurface area for the exchange of gases by diffusion along theirconcentration gradients. After a breath of air is inhaled into thelungs, it dilutes the CO₂ that remains in the alveoli at the end ofexhalation. A concentration gradient is then established between thepartial pressure of CO₂ (PCO₂) in the mixed venous blood (PvCO₂)arriving at the alveoli and the alveolar PCO₂. The CO₂ diffuses into thealveoli from the mixed venous blood from the beginning of inspiration(at which time the concentration gradient for CO₂ is established) untilan equilibrium is reached between the PCO₂ in blood from the pulmonaryartery and the PCO₂ in the alveolae at some time during breath. Theblood then returns to the heart via the pulmonary veins and is pumpedinto the arterial system by the left ventricle of the heart. The PCO₂ inthe arterial blood, termed arterial PCO₂ (PaCO₂) is then the same as wasin equilibrium with the alveoli. When the subject exhales, the end ofhis exhalation is considered to have come from the alveoli and thusreflects the equilibrium CO₂ concentration between the capillaries andthe alveoli. The PCO₂ in this gas is the end-tidal PCO₂ (P_(ET)CO₂). Thearterial blood also has a PCO₂ equal to the PCO₂ at equilibrium betweenthe capillaries and alveoli.

With each exhaled breath some CO₂ is eliminated and with eachinhalation, fresh air containing no CO₂ is inhaled and dilutes theresidual equilibrated alveolar PCO₂, establishing a new gradient for CO₂to diffuse out of the mixed venous blood into the alveoli. The rate ofbreathing, or ventilation (V_(E)), usually expressed in L/min, isexactly that required to eliminate the CO₂ brought to the lungs andestablish an equilibrium P_(ET)CO₂ and PaCO₂ of approximately 40 mmHg(in normal humans). When one produces more CO₂ (e.g. as a result offever or exercise), more CO₂ is carried to the lungs and one then has tobreathe harder to wash out the extra CO₂ from the alveoli, and thusmaintain the same equilibrium PaCO₂. But if the CO₂ production staysnormal, and one hyperventilates, then excess CO₂ is washed out of thealveoli and the PaCO₂ falls.

It is important to note that not all V_(E) contributes to elimination ofCO₂. The explanation for this is with reference to the schematic in thelung depicted in FIG. 10. The lung contains two regions that do notparticipate in gas equilibration with the blood. The first comprises theset of conducting airways (trachea and bronchi) 100 that act as pipesdirecting the gas to gas exchanging areas. As these conducting airwaysdo not participate in gas exchange they are termed anatomic dead space102 and the portion of V_(E) ventilating the anatomic dead space istermed anatomic dead space ventilation (V_(Dan)). The same volume ofinhaled gas resides in the anatomic dead space on each breath. The firstgas that is exhaled comes from the anatomic dead space and thus did notundergo gas exchange and therefore will have a gas composition similarto the inhaled gas. The second area where there is no equilibration withthe blood comprises the set of alveoli 103 that have lost their bloodsupply; they are termed alveolar dead space 104. The portion of V_(E)ventilating the alveolar dead space is termed alveolar dead spaceventilation (V_(Dalv)). Gas is distributed to alveolar dead space inproportion to their number relative to that of normal alveoli (normalalveoli being those that have blood vessels and participate in gasexchange with blood). That portion of V_(E) that goes to well perfusedalveoli and participates in gas exchange is called the alveolarventilation (V_(A)). In FIG. 10, the numeral references 105 and 106indicate the pulmonary capillary and the red blood cell, respectively.

Prior art circuits used to prevent decrease in PCO₂ resulting fromincreased ventilation, by means of rebreathing of previously exhaled gasare described according to the location of the fresh gas inlet,reservoir and pressure relief valve with respect to the patient. Theyhave been classified by Mapleson and are described in Dorsch and Dorschpg 168.

Mapleson A

The circuit comprises a pressure relief valve nearest to the patient, atubular reservoir and fresh inlet distal to the patient. In thiscircuit, on expiration, dead space gas is retained in the circuit, andafter the reservoir becomes full, alveolar gas is lost through therelief valve. Dead space gas is therefore preferentially rebreathed.Dead space gas has a PCO₂ much less than PaCO₂. This is less effectivein maintaining PCO₂ than rebreathing alveolar gas, as occurs with thecircuit of the present invention.

Mapleson B and C

The circuit includes a relief valve nearest the patient, and a reservoirwith a fresh gas inlet at the near patient port. As with Mapleson A deadspace gas is preferentially rebreathed when minute ventilation exceedsfresh gas flow. In addition, if minute ventilation is temporarily lessthan fresh gas flow, fresh gas is lost from the circuit due to theproximity of the fresh gas inlet to the relief valve. Under theseconditions, when ventilation once again increases, there is nocompensation for transient decrease in ventilation as the loss of freshgas will prevent a compensatory decrease in PCO₂.

Mapleson D and E

Mapleson D consists of a circuit where fresh gas flow enters near thepatient port, and gas exits from a pressure relief valve separated fromthe patient port by a length of reservoir tubing. Mapleson E is similarexcept it has no pressure relief valve allowing the gas to simply exitfrom an opening in the reservoir tubing. In both circuits, fresh gas islost without being first breathed. The volume of gas lost without beingbreathed at a given fresh flow is dependent on the pattern of breathingand the total minute ventilation. Thus the alveolar ventilation and thePCO₂ level are also dependent on the pattern of breathing and minuteventilation. Fresh gas is lost because during expiration, fresh gasmixes with expired gas and escapes with it from the exit port of thecircuit. With the present invention, all of the fresh gas is breathed bythe subject.

There are many different possible configurations of fresh gas inlet,relief valve, reservoir bag and CO₂ absorber (see Dorsch and Dorsch, pg.205–207). In all configurations, a mixture of expired gases enters thereservoir bag, and therefore rebreathed gas consists of combined deadspace gas and alveolar gas. This is less efficient in maintaining PCO₂constant than rebreathing alveolar gas preferentially as occurs with ourcircuit, especially at small increments of V above the fresh gas flow.

BRIEF SUMMARY OF THE INVENTION

The present invention comprises a method and a circuit that maintains aconstant PCO₂. More particularly, the present invention maintains aconstant PCO₂ by:

1) setting FGF equal to the baseline minute ventilation less theanatomical dead space ventilation (V_(Dan)); and

2) establishing PrgCO₂ being equal to the PaCO₂ rather than the PvCO₂ toincrease accuracy of the methods herein disclosed.

In the present invention, when minute ventilation is temporarily lessthan fresh gas flow, no fresh gas is lost from the circuit. Instead, thereservoir acts as a buffer to store extra fresh gas. When ventilationincreases once more, the subject breathing the accumulated fresh gasallows PCO₂ to return to the previous level.

A circuit to maintain isocapnia is also provided by the invention. Thecircuit includes a non rebreathing valve, a source of fresh gas, a freshgas reservoir and a source of gas to be inhaled when minute ventilationexceeds fresh gas flow. Preferably, the flow of fresh gas is equal tominute ventilation minus anatomic dead space. Any additional inhaled gasexceeding fresh gas flow has a partial pressure of CO₂ equal to thepartial pressure of CO₂ of arterial blood.

The invention further provides a method of measuring anatomical and/oralveolar dead space ventilation by using a breathing circuit consistingof a non rebreathing valve, a source of fresh gas, a fresh gas reservoirand a source of gas with a partial pressure of CO₂ substantially equalto that of arterial blood.

In one embodiment of the invention, the non-rebreathing circuitcomprises an exit port, a non-rebreathing valve, a source of fresh gas,a fresh gas reservoir, and a reservoir gas supply. From the exit port,gases are supplied from the circuit to the patient. The non-rebreathingvalve has a one-way valve permitting gases to be delivered to the exitport to the patient, but prevents gases from passing into the circuit.The source of fresh gas may be oxygen, air or the like excluding CO₂(air containing physiologically insignificant amount of CO₂) and is incommunication with the non-rebreathing valve to be delivered to thepatient. The fresh gas reservoir is in communication with the source offresh gas flow for receiving excess fresh gas not breathed by thepatient from the source of fresh gas and for storage thereof, wherein asthe patient breathes gas from the source of fresh gas flow and from thefresh gas reservoir are available depending on the minute ventilationlevel. The reserve gas supply contains CO₂ and other gases (usuallyoxygen) preferably having a partial pressure of the CO₂ approximatelyequal to the partial pressure of CO₂ in the arterial blood of thepatient. The reserve gas supply is delivered to the non-rebreathingvalve to make up that amount of gas required by the patient forbreathing that is not fulfilled from the gases delivered from the sourceof fresh gas flow and the fresh gas reservoir. The source of gas, thefresh gas reservoir and the reserve gas supply are disposed on the sideof the non-breathing valve remote from the exit port.

Preferably, a pressure relief valve is provided in the circuit incommunication with the fresh gas reservoir in the event that the freshgas reservoir overfills with gas so that the fresh gas reservoir doesnot break, rupture or become damaged in any way.

The reserve gas supply preferably includes a demand valve regulator.When additional gas is required, the demand valve regulator opens thecommunication of the reserve gas supply to the non-rebreathing valve fordelivery of the gas thereto. When additional gas is not required, thedemand valve regulator is closed and only fresh gas flows from thesource of fresh gas and from the fresh gas reservoir to thenon-rebreathing valve. The source of fresh gas is set to supply freshgas (non-CO₂-containing gas) at a rate equal to desired alveolarventilation for the elimination of CO₂, that is, the baseline minuteventilation minus anatomical dead space.

The basic concept of the present invention is when breathing increases,flow of fresh gas (inspired PCO₂=0) from the fresh gas flow contributingto elimination of CO₂ is kept constant, and equal to the baseline minuteventilation minus anatomical dead space. The remainder of the gasinhaled by the subject (from the reserve gas supply) has a PCO₂ equal tothat of arterial blood, resulting in the alveolar PCO₂ stabilizing atthe arterial PCO₂ level regardless of the level of ventilation as longas minute ventilation minus anatomical dead space is greater than thefresh gas flow. In the event that the desired PaCO₂ is a particularvalue, which may be higher or lower than the initial PaCO₂ of thesubject, then the PCO₂ having an adjustable feature of the reserve gasmay simply be set equal to the desired PaCO₂. If the PaCO₂ isspecifically desired to remain equal to the initial PaCO₂ of thesubject, then the PaCO₂ can be measured by obtaining a sample ofarterial blood from any artery, and the PCO₂ of the reserve gas setequal to this valve. Alternatively, an estimation of the PaCO₂ can bemade from P_(ET)CO₂. P_(ET)CO₂ is determined by measuring the PCO₂ ofexpired breath using a capnograph usually present or easily available inmedical and research facilities to persons skilled in the art.

In effect, the present invention passively causes the amount of CO₂breathed in by the patient to be proportional to the amount of totalbreathing, thereby preventing any perturbation of the arterial PCO₂.This is unlike prior art servo-controllers which always attempt tocompensate for changes. Persons skilled in the art, however, may chooseto automate the circuit by using a servo-controller or computer tomonitor minute ventilation levels and deliver inspired gas with theconcentrations of CO₂ substantially equal to that of those from freshgas and reserve gas were the gases mixed together.

The non-rebreathing circuit provided by the present invention can alsobe used to enable a patient to recover more quickly from, and to hastenthe recovery of the patient after vapor anaesthetic administration, orpoisoning with carbon monoxide, methanol, ethanol, or other volatilehydrocarbons.

According to another aspect of the invention, a method of treatment ofan animal or person is provided. The method comprises delivering to apatient gases which do not contain CO₂ at a specific rate, and gasescontaining CO₂ to maintain the same PCO₂ in the patient, at the rate ofventilation of the patient which exceeds the rate of administration ofthe gases which do not contain CO₂ independent of the rate ofventilation.

The circuit and method of treatment can also be used for anycircumstance where it is desirable to dissociate the minute ventilationfrom elimination of carbon dioxide such as respiratory muscle training,investigation of the role of pulmonary stretch receptors,tracheobronchial tone, expand the lung to prevent atelectasis, exercise,and control of respiration and other uses as would be understood bythose skilled in the art.

The circuit and method of treatment of the present invention may also beused by deep sea divers and astronauts to eliminate nitrogen from thebody. It can also be used to treat carbon monoxide poisoning under normabaric or hyper baric conditions. In this case, the fresh gas wouldcontain a higher concentration of oxygen than ambient air, for example,100% O₂, and the reserve gas will contain approximately 5.6% CO₂ and ahigh concentration of oxygen, for example, 94% of O₂.

In another embodiment of the invention, a method of controlling PCO₂ ina patient at a predetermined desired level is provided comprising abreathing circuit which is capable of organizing exhaled gas so as to bepreferentially inhaled during re-breathing when necessary by providingalveolar gas for re-breathing in preference to dead space gas. Thepreferred circuit in effecting this method includes a breathing port forinhaling and exhaling gas, a bifurcated conduit adjacent to the port.The bifurcated conduit has a first and a second conduit branches. Thefirst conduit has a fresh gas inlet and a check valve allowing thepassage of inhaled fresh gas to the port but closing during exhalation.The second conduit branch includes a check valve which allows passage ofexhaled gas through the check valve but prevents flow back to the port.A fresh gas reservoir is located at the terminus of the first conduitbranch, while an exhaled gas reservoir is located at the terminus of thesecond conduit branch. An interconnecting conduit having a check valvetherein is located between the first and the second conduit branches toresult in the fresh flow gas in the circuit equal to baseline minuteventilation minus ventilation of anatomic dead space for the patient. Inthe exhaled gas reservoir, the exhaled gas is preferably disposednearest the open end thereof, and the alveolar gas is located proximatethe end of the reservoir nearest the terminus of the second conduitbranch, so that the shortfall differential of PCO₂ is made of alveolargas being preferentially rebreathed, thereby preventing a change in thePCO₂ level of alveolar gas despite the increased minute ventilation.

It is important to set up the fresh gas flow to be baseline minuteventilation minus anatomic dead space ventilation. In this way, once itis desired to increase the minute ventilation, a slight negativepressure will exist in the interconnecting conduit during inhalation,opening its check valve and allowing further breathing beyond the normallevel of ventilation to be supplied by previously exhaled gas.

The present invention also provides a method of enhancing the results ofa diagnostic procedure or medical treatment. A circuit which is capableof organizing exhaled gas so as to provide to the patient preferentialrebreathing of alveolar gas in preference to dead space gas is provided.The patient is ventilated when a rate greater than the fresh gas flow isdesired, and when hypercapnia is desired to induce. The fresh gas flowis passively decreased to provide a corresponding increase in rebreathedgas. The hypercapnia is continuously induced until the diagnostic ormedical procedure is complete. Examples of the medical procedureincludes MRI, radiation treatment or the like.

The present invention can also be applied to treat or assist a patient,preferably human, during a traumatic event characterized byhyperventilation. A breathing circuit in which alveolar ventilation isequal to the fresh gas flow and increases in alveolar ventilation withincreases in minute ventilation is prevented, is provided. The circuitis capable of organizing exhaled gas provided to the patient andpreferential rebreathing alveolar gas in preference to dead space gasfollowing ventilating the patient at a rate of normal minuteventilation, preferably approximately 5 L per minute. When desired,hypercapnia is induced to increase arterial PCO₂ and prevent the PCO₂level of arterial blood from dropping. The normocapnia is maintaineddespite the ventilation is increased until the traumatichyperventilation is complete. As a result, the effects ofhyperventilation experienced during the traumatic event are minimized.This can be applied when a mother is in labor and becomes light headedor when the baby during the delivery is effected with the oxygendelivery to its brain being decreased as a result of contraction of theblood vessels in the placenta and fetal brain. A list of circumstancesin which the method enhancing the diagnostic procedure results or theexperience of the traumatic even are listed below.

Applications of the method and circuit includes:

-   1) Maintenance of constant PCO₂ and inducing changes in PCO₂ during    MRI.-   2) Inducing and/or marinating increased PCO₂:    -   a) to prevent or treat shivering and tremors during labor,        post-anesthesia, hypothermia, and certain other pathological        states;    -   b) to treat fetal distress due to asphyxia;    -   c) to induce cerebral vasodilatation, prevent cerebral        vasospasm, and provide cerebral protection following        subarachnoid hemorrhage cerebral trauma and other pathological        states;    -   d) to increase tissue perfusion in tissues containing cancerous        cells to increase their sensitivity to ionizing radiation and        delivery of chemotherapeutic agents;    -   e) to aid in radio diagnostic procedures by providing contrast        between tissues with normal and abnormal vascular response; and    -   f) protection of various organs such as the lung, kidney and        brain during states of multi-organ failure.-   3) Prevention of hypocapnia with O₂ therapy, especially in pregnant    patients.-   4) Other applications where O₂ therapy is desired and it is    important to prevent the accompanying drop in PCO₂.

By carrying out the above method and preferably with the above circuit,an improved method of creating MRI images is disclosed to maintain aconstant PCO₂ and induce changes in that PCO₂ level during the MRIprocedure in order to facilitate improvement in the quality of theimages being obtained. The prior art Mapleson D and E circuitspredictably may work with the method of the present invention as well asa standard circuit with the carbon dioxide filter bypassed or removed;however fresh gas will be wasted and the efficiency would be reduced.

A method of delivering to a patient, preferably human, inhaled drugssuch as gases, vapors or suspensions of solid particles, particles ordroplets, for example, nitric oxide, anesthetic vapors, bronchodilatorsor the like, using the above circuit to increase the efficiency ofdelivery allows the quantification of the exact dose.

A method of delivering to a patient, preferably human, pure oxygen isprovided. The circuit described above increases the efficiency ofdelivery because all the fresh gas is inhaled by the patient, or todeliver the oxygen to the patient in a more predictable way, allowingthe delivery of a precise concentration of oxygen.

When minute ventilation minus anatomical dead space ventilation isgreater than or equal to fresh gas flow, the above circuit prevents lossof fresh gas and ensures that the patient receives all the fresh gasindependent of the pattern of breathing since fresh gas alone enters thefresh gas reservoir, and exhaled gas enters its own separate reservoir.The fresh gas reservoir bag is large enough to store fresh gas for 5–10seconds or more of reduced ventilation or total apnea, ensuring thateven under these circumstances fresh gas will not be lost. The preferredcircuit prevents rebreathing at a minute ventilation equal to the freshgas flow because the check valve in the interconnecting conduit does notopen to allow rebreathing of previously exhaled gas unless a negativepressure exist on the inspiratory side of the conduit of the circuit.Also, when minute ventilation exceeds the fresh gas flow, a negativepressure occurs in the inspiratory conduit, opening the conduit's checkvalve. The circuit provides that after the check valve opens, alveolargas is rebreathed in preference to dead space gas because theinterconnecting conduit is located such that exhaled alveolar gas willbe closest to it and dead space gas will be further from it. When thefresh gas flow is equal to VE−V_(Dan), the volume of rebreathed gas willventilate the anatomical dead space only, leaving the alveolarventilation unchanged. The exhaled gas reservoir is preferably sized at3 L which is well in excess of the volume of an individual's breath,therefore it is unlikely that the patient shall be able to breathe anyroom air entering via the opening at the end of the exhaled gasreservoir.

The basic approach of preventing a decrease in PCO₂ with increasedventilation is similar to that of the non-rebreathing system. In brief,only the fresh gas contributes to alveolar ventilation (V_(A)) whichestablishes the gradient for CO₂ elimination. All gas breathed in excessof the fresh gas entering the circuit, or the fresh gas flow, isrebreathed gas. The terminal part of the exhaled gas contains gas thathas been in equilibrium with arterial blood and hence has a PCO₂substantially equal to arterial blood. The Fisher (WO98/41266) patentteaches that the closer PCO₂ in the inhaled gas to PvCO₂, the less theeffect on CO₂ elimination. Yet, it would not maintain a constant PaCO₂as V_(E) increases. The present invention discloses that the greater theventilation of gas with a PCO₂ equal to PvCO₂, the closer the PaCO₂ getsto PvCO₂. The present invention also discloses that when PCO₂ of inhaledgas is substantially equal to PaCO₂, increased ventilation will not tendto change the PaCO₂. Since the terminal part of the exhaled gas containsgas that has been in equilibrium with arterial blood and hence has aPCO₂ substantially equal to arterial blood, the PaCO₂ will be unchangedregardless of the extent of rebreathing.

With the use of the circuit of the present invention:

-   1. All of the fresh gas is inhaled by the subject when minute    ventilation minus anatomical dead space is equal to or exceeds fresh    gas flow.-   2. The “alveolar gas” is preferentially rebreathed when minute    ventilation minus anatomical dead space exceeds the fresh gas flow.-   3. When minute ventilation minus anatomical dead space is equal to    or greater than fresh gas flow, all the fresh gas contributes to    alveolar ventilation.

In another embodiment of the invention, a method of establishing aconstant flow of fresh gas in the form of atmospheric air forced as aresult of breathing efforts by the patient, but independent of theextent of ventilation, is provided. The flow is delivered into abreathing circuit such as that taught by Fisher et al.,(non-rebreathing) designed to keep the PCO₂ constant by providingexpired gas to be inhaled when the minute ventilation exceeds the flowof fresh gas. Furthermore, there is provided a compact expired gasreservoir capable of organizing exhaled gas so as to be preferentiallyinhaled during rebreathing when necessary by providing alveolar gas forre-breathing in preference to dead space gas. The preferred circuit ineffecting the above-mentioned method includes a breathing port forinhaling and exhaling gas, a bifurcated conduit adjacent to the port insubstantially a Y-shape. The bifurcated conduit has a first and a secondconduit branches. The first conduit has an atmospheric air inlet theflow through which is controlled by a resistance for example that beingprovided by a length of tubing, and a check valve allowing the passageof inhaled atmospheric air to the port but closing during exhalation.The second conduit branch includes a check valve which allows passage ofexhaled gas through the check valve but prevents flow back to the port.An atmospheric air aspirator (AAA) is located at the terminus of thefirst conduit branch, while an exhaled gas reservoir of about 3 L incapacity is located at the terminus of the second conduit branch. TheAAA comprises a collapsible container tending to recoil to openposition. An interconnecting conduit having a check valve therein islocated between the first and the second conduit branches. When minuteventilation minus anatomic dead space ventilation is equal to the rateof atmospheric air aspirated into the circuit, for example, 4 L perminute, atmospheric air enters the breathing port from the first conduitbranch at a predetermined rate and preferably 4 L per minute. Meanwhile,the exhaled gas at a rate of 4 L per minute travels town to the exhaledgas reservoir. When it is desirable for the minute ventilation to exceedthe fresh gas flow, for example, 4 L per minute, the patient will inhaleexpired gas retained in the expired gas reservoir through theinterconnecting conduit at a rate making up the shortfall of theatmospheric air.

While setting the fresh gas flow to maintain a desired PCO₂, it isimportant to set up the atmospheric air aspirator be allowed to first bedepleted of gas until it just empties at the end of the inhalationcycle. In this way, once it is desired to increase the minuteventilation, the increased breathing effort required to do so willfurther decrease the sub-atmospheric pressure in the first conduitbranch, being the inspiratory limb, and open the check valve in theinterconnecting conduit to allow further breathing of gas beyond thelevel of ventilation supplied by the volume of atmospheric air aspiratedinto the circuit during the entire breathing cycle.

The circuit of the present invention is particularly applicable whenatmospheric air is a suitable form of fresh gas and when it isinconvenient or impossible to access a source of compressed gas or airpump to provide the fresh gas flow. During mountain climbing or workingat high altitude, some people tend to increase their minute ventilationto an extent greater than that required to optimize the alveolar oxygenconcentration. This will result in an excessive decrease in PCO₂ whichwill in turn result in an excessive decrease in flood flow and henceoxygen delivery to the brain. By using the above circuit at highaltitude a limit can be put on the extent of decrease in PCO₂ and thusmaintain the oxygen delivery to the brain in the optimal range.

During resuscitation of an asphyxiated newborn or an adult suffering acardiac arrest, the blood flow through the lungs is remarkably slowduring resuscitation attempts. Even normal rates of ventilation mayresult an excessive elimination of CO₂ from the blood. As the bloodreaches brain, the low PCO₂ may constrict the blood vessels and limitthe potential blood flow to the ischemic brain. By attaching theisocapnia circuit provided by the invention to the gas inlet port of aresuscitation bag and diverting all expiratory gas to the expiratory gasreservoir bag, the decrease of PCO₂ would be limited.

The isocapnia circuit of the present invention can be applied to enhancethe results of a diagnostic procedure or a medical treatment byproviding a circuit without a source of forced gas flow and beingcapable of organizing exhaled gas. With the circuit, preferentialrebreathing of alveolar gas in preference to dead space gas is providedwhen the patient is ventilating at a rate greater than the rate ofatmospheric air aspirated, and when inducing hypercapnia is desired. Bydecreasing the rate of aspirated atmospheric air, a correspondingincrease in rebreathed gas is passively provided to prevent the PCO₂level of arterial blood from dropping despite increase in minuteventilation. The step of inducing hypercapnia is continued until thediagnostic or medical therapeutic procedure is complete. The results ofthe diagnostic or medical procedure are thus enhanced by carrying outthe method in relation to the results of the procedure had the methodnot been carried out. Examples of such procedures include MRI orpreventing spasm of brain vessels after brain hemorrhage, radiationtreatments or the like.

The present invention can also be applied to treat or assist a patient,preferably human, during a traumatic event characterized byhyperventilation. A circuit that does not require a source of forced gasflow, in which alveolar ventilation is equal to the rate of atmosphericair aspirated and increases in alveolar ventilation with increases inminute ventilation is prevented, is provided. For example, the isocapniacircuit as described above, is capable of organizing exhaled gasprovided to the patient preferential rebreathing alveolar gas inpreference to dead space gas following ventilating the patient at a rateof normal minute ventilation, preferably approximately 5 L per minute.When desired, hypercapnia is induced to increase arterial PCO₂ andprevent the PCO₂ level of arterial blood from dropping. The normocapniais maintained despite the ventilation being increased until thetraumatic hyperventilation is complete. As a result, the effects ofhyperventilation experienced during the traumatic event are minimized.This can be applied when a mother is in labor and becomes light headedor the baby during the delivery is effected with the oxygen delivery toits brain being decreased as a result of contraction of the bloodvessels in the placenta and fetal brain. A list of circumstances inwhich the method enhancing the diagnostic procedure results or theexperience of the traumatic even are listed below.

Applications of the method and circuit includes:

-   1) Maintenance of constant PCO₂ and inducing changes in PCO₂ during    MRI.-   2) Inducing and/or marinating increased PCO₂:    -   a) to prevent or treat shivering and tremors during labor,        post-anesthesia, hypothermia, and certain other pathological        states;    -   b) to treat fetal distress due to asphyxia;    -   c) to induce cerebral vasodilatation, prevent cerebral        vasospasm, and provide cerebral protection following        subarachnoid hemorrhage cerebral trauma and other pathological        states;    -   d) to increase tissue perfusion in tissues containing cancerous        cells to increase their sensitivity to ionizing radiation and        delivery of chemotherapeutic agents;    -   e) to aid in radio diagnostic procedures by providing contrast        between tissues with normal and abnormal vascular response; and    -   f) protection of various organs such as the lung, kidney and        brain during states of multi-organ failure.-   3) Prevention of hypocapnia with O₂ therapy, especially in pregnant    patients.-   4) Other applications where O₂ therapy is desired and it is    important to prevent the accompanying drop in PCO₂.

When minute ventilation is greater than or equal to the rate ofatmospheric air aspirated, the above-mentioned preferred circuit ensuresthat the patient receives all the atmospheric air aspirated into thecircuit, independent of the pattern of breathing; since atmospheric airalone enters the fresh gas reservoir and exhaled gas enters its ownseparate reservoir and all the aspirated air is delivered to the patientduring inhalation before rebreathed exhaled gas. The atmospheric airaspirator preferably large enough not to fill to capacity duringprolonged exhalation, when the total minute ventilation exceeds the rateof atmospheric air aspiration ensuring that under these circumstancesatmospheric air continues to enter the circuit uninterrupted duringexhalation. The preferred circuit prevents rebreathing at a minuteventilation equal to the rate of air being aspirated into theatmospheric air aspirator because the check valve in the interconnectingconduit does not open to allow rebreathing of previously exhaled gasunless a sub-atmospheric pressure less than that generated by the recoilof the aspirator exists on the inspiratory side of the conduit of thecircuit. The circuit provides that after the check valve opens, alveolargas is rebreathed in preference to dead space gas because theinterconnecting conduit is located such that exhaled alveolar gascontained in the tube conducting the expired gas into the expiratoryreservoir bag will be closest to it and dead space gas will be mixedwith other exhaled gases in the reservoir bag. In the preferredembodiment, the exhaled gas reservoir is preferably sized at about 3 Lwhich is well excess of the volume of an individual's breath. When thepatient inhales gas from the reservoir bag, the reservoir bag collapsesto displace the volume of gas extracted from the bag, minimizing thevolume of atmospheric air entering the bag.

The basic approach of the present invention to prevent a decrease inPCO₂ with increase ventilation is to arrange that the fresh gas enters,the circuit at a rate equal to the desired minute ventilation minusanatomic dead space ventilation. In brief, breathing only fresh gascontributes to alveolar ventilation (V_(A)) which establishes thegradient for CO₂ elimination. All gas breathed in excess of the freshgas entering the circuit, or the fresh gas flow, is rebreathed gas. Thecloser the partial pressure of carbon dioxide in the inhaled gas to thatof arterial blood, the less the effect on CO₂ elimination. Withincreased levels of ventilation, greater volumes of previously exhaledgas are breathed. The rebreathed gas has a PCO₂ substantially equal tothat of arterial blood, thus contributing little if anything to alveolarventilation, and allowing the P_(ET)CO₂ and PaCO₂ to change little.

Further, if the fresh gas flow is equal to the minute ventilation minusthe anatomic dead space ventilation, when minute ventilation is equal toor exceeds the rate of atmospheric air aspirated into the circuit, thenall of the delivered fresh gas remains constant and equal to the restingalveolar ventilation. The “alveolar gas” is preferentially rebreathedwhen minute ventilation exceeds the fresh gas flow. These, as well asother features of the present invention will become more evident uponreference to the drawings and detailed description of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates schematically the nature of the simplenon-rebreathing circuit and components which enable the patient torecover more quickly from vapor anaesthetics or other volatile agents.The device enables the arterial or end-tidal PCO₂ to remain relativelyconstant despite increase in minute ventilation which thereby permitsfaster elimination of the vapor anaesthetic or other volatile compounds;

FIG. 2 illustrates schematically portions of a standard circleanaesthetic;

FIG. 3 illustrates schematically the simple non-rebreathing circuit inone embodiment added to portions of the circle anaesthetic circuit shownschematically in FIG. 2, illustrating modifications of the circuit shownschematically in FIG. 1 for use with the circuit shown in FIG. 2;

FIG. 4A illustrates the structure shown in FIG. 3 combined with thestructure shown in FIG. 2;

FIGS. 4B and 4C illustrate schematically close up portions of oneportion of the structure shown in FIG. 4A in different positions;

FIG. 5 depicts schematic representations of a lung at progressivelyincreasing ventilations (A–D). Gas in the alveolar compartment of thelung participates in gas exchange, and thus can contribute to theelimination of CO₂, whereas gas in the anatomical dead space does notcontribute to gas exchange. The hatched area indicates fresh gas; thestippled area indicates reserve gas;

FIG. 6 illustrates a mathematical model used to calculate PaCO₂ as afunction of minute ventilation;

FIG. 7 illustrates schematically the nature of the simple breathingcircuit and components enabling the PCO₂ to remain constant despite increase in minute ventilation;

FIG. 8 illustrates a graph of how FGF flow may be slowly decreasedaffecting P_(ET)CO₂ exponentially in time;

FIG. 9 is a schematic view of the portable circuit of the invention; and

FIG. 10 is a schematic view of the lungs illustrating anatomical deadspace in relation to alveolar dead space.

DETAILED DESCRIPTION OF THE INVENTION

PCT Application No. WO98/41266 filed by Joe Fisher (WO98/41266) teachesa method of accelerating the resuscitation of a patient which has beenanaesthetized by providing the patient with a flow of fresh gas (FGF)and a source of reserve gas is expressly incorporated herein byreference. As thought in WO98/41266, when the patient breathes at a rateless than or equal to the fresh gas flowing into the circuit, all of theinhaled gas is made up of fresh gas. When the patient's minuteventilation exceeds the fresh gas flow, the inhaled gas is made up ofall of the fresh gas and the additional gas is provided by “reserve gas”with a composition similar to the fresh gas but with CO₂ added such thatthe concentration of CO₂ in the reserve gas of about 6% is such that itspartial pressure is equal to the partial pressure of CO₂ in the mixedvenous blood. At no time while using this method will the patientrebreathe gas containing anaesthetic. In order to accelerate theresuscitation of the patient, a source of fresh gas is provided fornormal levels of minute ventilation, typically 5 L per minute and asupply of reserve gas is provided for levels of ventilation above 5 Lper minute wherein the source of reserve gas includes approximately 6%carbon dioxide having a PCO₂ level substantially equal to that of mixedvenous blood.

Although Fisher's WO98/41266 method prevents significant variations inP_(ET)CO₂, it cannot keep PCO₂ precisely constant as a result of twoimperial approximations in the method:

-   -   a) Setting FGF equal to the baseline minute ventilation as        Fisher taught is excessive to keep the PaCO₂ from decreasing,        since with increased ventilation, fresh gas from the anatomic        dead space enters the alveoli providing increased alveolar        ventilation which tends to lower PaCO₂.    -   b) Setting PrgCO₂ substantially equal to PvCO₂ prevents the        elimination of CO₂ and tends to increase PaCO₂ towards PrgCO₂ as        ventilation increases.

The proof assumes the same circuit described by Fisher, where a flow offresh gas with a PCO₂ of 0 is set equal to Verest, and the balance ofV_(E) consists of reserve gas with a PCO₂ of PrgCO₂. This proof willshow that PrgCO₂ should be equal to PaCO₂, and not to PvCO₂ aspreviously approximated in order for P_(ET)CO₂ to remain constant forany increase in V_(E).

In pending application (Fisher I A, Vessely A., Sasano H., Volyesi G.,Tesler J.: entitled Improved Rebreathing Circuit for MaintainingIsocapnia), filed in Canada March 2000 and in the USA in October 2000 asSer. No. 09/676,899, the disclosure of which is expressly incorporatedherein by reference) there is described a method of simplifying thecircuit taught by Fisher (WO98/41266), wherein the reserve gas may bereplaced by previously exhaled gas. The first filed Fisher applicationteaches that the fresh gas flow is set equal to minute ventilation toprevent change in P_(ET)CO₂ and PaCO₂. This is not optimal to preventchanges P_(ET)CO₂ and PaCO₂ since as minute ventilation increases, thefresh gas previously residing in the trachea exhaled without engaging ingas exchange can then be inhaled into the alveoli and hence adds to gasexchange and thus P_(ET)CO₂ and PaCO₂ which will equilibrate to a valvelower than those at rest.

However, the present invention teaches that to prevent changes inP_(ET)CO₂ and PaCO₂ the fresh gas flow should be substantially equal tothe baseline ventilation minus the anatomic dead space ventilation.

Pending Canadian application Serial No. 2,340,511 filed by Fisher onMar. 31, 2000 entitled A Portable Partial Rebreathing Circuit to Set andStabilize End Tidal and Arterial PCO₂ Despite Varying Levels of MinuteVentilation which is also incorporated herein by reference describes acircuit a circuit that exploits the same principle in maintaining PCO₂constant; however, it replaces the fresh gas reservoir bag with asubstantially flexible container which is actively collapsed by theinspiratory effort of the patient during inspiration and passivelyexpands during expiration drawing into itself and the circuitatmospheric air through a port provided for that purpose. The expiratoryreservoir is provided with a flexible bag so that the volume of expiredgas rebreathed is displaced by collapse of the bag rather thanentrainment of atmospheric air, thus preventing the dilution of CO₂ inthe expired gas reservoir.

It is the primary object of the present invention to form a portablecircuit to reap the benefits of controlling the PCO₂ at a constant leveland not having to incur the expense and inconvenience of supplying freshgas. Furthermore the compact nature of the present invention will makeits use practical outdoors, during physical activity and in remoteenvironments, for example, for the resuscitation of newborns with airyet preventing an excessive decrease in PCO₂. In the prior art Fisherteaches that the total fresh gas flow into the bellows should be equalto minute ventilation. This again is not optimal to prevent changesP_(ET)CO₂ and PaCO₂ since as minute ventilation increases, the fresh gaspreviously residing in the trachea exhaled without an opportunity toengage in gas exchange can now be inhaled into the alveoli and add togas exchange and thus P_(ET)CO₂ and PaCO₂ will equilibrate to a valuelower than those at rest.

FIG. 1 shows a non-rebreathing circuit. In FIG. 1, a non-rebreathingvalve 10 is connected distally to two ports 11 and 12. The port 12 isconnected in parallel to a source of fresh gas 13 (which does notcontain CO₂) and a fresh gas reservoir 14. A one-way pressure reliefvalve 15 prevents overfilling of the reservoir 14 by venting excessfresh gas. The port 11 is connected via a one-way valve 16 to a sourceof gas (containing CO₂) whose PCO₂ is equal approximately to that of thearterial PCO₂. The source of gas is called the reserve gas and denotedby a reference numeral 17. The non-rebreathing valve 10 is furtherconnected to an exit port 18, from which the subject or the patientbreathes.

FIG. 5 depicts schematic representations of a lung at progressivelyincreasing ventilation (A–D). Gas in the alveolar compartment of thelung participates in gas exchange, and thus can contribute to theelimination of CO₂, whereas gas in the anatomical dead space does notcontribute to gas exchange. The hatched area indicates fresh gas; thestippled area indicates reserve gas.

V_(E) is the total amount of gas ventilation the lung, including boththe alveolar compartment and the anatomical dead space. V_(D)an is theamount of gas ventilating just the anatomical dead space. Therefore,V_(E)−V_(D)an is the amount of gas available for ventilating thealveolar compartment, i.e., the amount of gas which can contribute togas exchange (alveolar ventilation, V_(A)).

When V_(E)−V_(D)an is less than or equal to the fresh gas flow “FGF”from the source of fresh gas flow 13, only fresh gas (non-CO₂-containinggas) enters the alveolar compartment. When V_(E)−V_(D)an exceeds FGF,the reservoir 14 containing fresh non-CO₂-containing gas empties firstand the balance of inhaled gas is drawn from the reserve gas 17 whichcontains a specific concentration of CO₂. If minute ventilation exceedsFGF, the difference between minute ventilation and fresh gas flow ismade up of gas from the reserve gas source 17 which contains CO₂ at apartial pressure which, being substantially the same as that in thearterial blood, eliminates any gradient for diffusion of CO₂ between thetwo compartments. For example, if the FGF is 3 L per minute and thesubject breathes at 5 L per minute or less, then the patient will inhaleonly non-CO₂-containing gas that comes from the source(s) of the freshgas flow 13 and 14. In this case, a proportion of the fresh gas willventilate the alveolar compartment (for example, at 4 L per minute) andthe remainder of the fresh gas will ventilate the anatomical dead space(for example, at 1 L/min). Thus V_(E)−V_(D)an establishes the maximumpotential alveolar ventilation (V_(A)).

When FGF is set exactly equal to V_(E)−V_(D)an (FIG. 5, panel C), freshgas, and only fresh gas provides all the V_(A). Therefore any increasein ventilation will result in reserve gas being the only additional gasdrawn into the alveolar compartment. To set the FGF, after firstapproximately matching the fresh gas flow to V_(E), the FGF can beslowly decreased, for example, in 200 mL/min decrements, withoutaffecting the PaCO₂ (FIG. 8). This is because the initial decreases inFGF decrease only the amount of FGF ventilating the anatomical deadspace, but not the alveolar compartment. At a certain point, which weterm the “inflection point”, any further decrease in FGF will decreasethe volume of fresh gas ventilating the alveolar compartment per unittime and PCO₂ will begin to rise exponentially. The inflection point isthe point at which FGF=V_(E)−V_(D)an, and represents the FGF required tomaintain PCO₂ constant.

Now considering the concentration of CO₂ which is required in thereserve gas in order to provide no ventilation. A mathematical model hasbeen used to calculate the PaCO₂ as a function of minute ventilation(FIG. 6). Note that for each FGF and PrgCO₂ tested, the PaCO₂, asventilation increases, approaches the PCO₂ of the reserve gas. Thisindicates that the appropriate reserve concentration is that equal tothe desired PaCO₂. (Curves 3 and 4). A system of equations belowconfirms that the reserve gas PCO₂ must be equal to the arterial PCO₂.

When ventilation approaches infinity, the PCO₂ of the gas in the alveoliwill approach the PrgCO₂. Since the PaCO₂ (for example 40 mmHg) is inequilibrium with the alveolar PCO₂, the PaCO₂ will approach the PrgCO₂which has been set at PvCO₂ (46 mmHg), and thus will not be maintainedat initial levels, for example 40 mmHg.

Clearly the PrgCO₂ cannot be set equal to PvCO₂. The present inventorshave determined the PrgCO₂ should instead be set equal to PaCO₂ in orderto maintain PaCO₂ unchanged at all levels of V_(E) above resting V_(E)(testing V_(E)). Although Fisher's method works well at low V_(E), thepresent invention offer the following improvement which works well atall V_(E), and in so doing provide a better explanation of theunderlying physiology.

FGF shall equal resting minute ventilation minus anatomical dead spaceventilation (V_(E)−V_(Dan)).

This proof assumes the same circuit described by Fisher, where a flow offresh gas with a PCO₂ of 0 is set equal to V_(E)rest, and the balance ofV_(E) consists of reserve gas with a PCO₂ of PrgCO₂. This proof willshow that PrgCO₂ should be equal to PaCO₂, and not to PvCO₂ aspreviously approximated in order for P_(ET)CO₂ to remain constant forany increase in V_(E).

In the above and following description,

-   P_(ET)CO₂ is defined as the end tidal partial pressure of carbon    dioxide (mmHg);-   Prest_(ET)CO₂ is the end tidal pressure of carbon dioxide (mmHg);-   PiCO₂ is the inspired partial pressure of carbon dioxide (mmHg);-   Pbar is the barometric pressure (mmHg);-   V_(E) is the minute ventilation (mL/min);-   VCO₂ is the volume of CO₂ produced in 1 minute (mL/min);-   VrestCO₂ is the volume of CO₂ produced at rest in 1 minute (mL/min);-   Verest is the minute ventilation at rest;-   n is the minute ventilation expressed as number of times minute    ventilation at rest;    n is equal to V _(E) /V _(E)rest, so that V _(E) =n*V _(E)rest  (1)    By specifying that VCO2 remains at VrestCO₂, so that VCO₂=VrestCO₂;    and P_(ET)CO₂ remains at Prest_(ET)CO₂, so that    P_(ET)CO₂=Prest_(ET)CO₂.

The difference between the inspired and expired PCO₂ (as a fraction ofthe barometric pressure) times the ventilation must be equal to the CO₂produced by the body in a given period of time (for example 1 minute).(Prest_(ET)CO₂ −PiCO₂)/Pbar*V _(E) =VrestCO₂  (2)With Fisher's circuit, inspired PCO₂ can be calculated for any n. Theinspired PCO₂ is an average of the PCO₂ of the fresh gas (0 mmHg) andthe reserve gas (PrgCO₂), weighted by the relative volumes inspired:PCO₂=(n−1)/n*PrgCO₂  (3)For example, at 4×V_(E)rest, inspired PCO₂ is ¾ reserve gas PCO₂,because reserve gas comprises ¾ of the total gas inspired, while theremaining ¼ is fresh gas which has a PCO₂ of 0.

Substitution of 1 and 3 into 2 gives((P _(ET)CO₂−(n−1)/n*PrgCO₂)/Pbar)*n*V _(E)rest=VrestCO₂)

Solving for PrgCO₂,P _(ET)CO₂−(n−1)/n*PrgCO₂ =VrestCO₂ *Pbar/(n*V _(E)rest)P _(ET)CO₂ −VrestCO₂ *Pbar/(n*V _(E)rest)=(n−1)/n*PrgCO₂(P _(ET)CO₂ −VrestCO₂ *Pbar/(n*V _(E)rest))*n/(n−1)=PrgCO₂PrgCO₂=(Prest_(ET)CO₂ −VrestCO₂ *Pbar/(n*Vrest))*n/(n−1)  (4)Now,(VCO₂ /V _(E))*Pbar=PrestETCO₂  (5)

Solving (5) for V_(E), we obtainV _(E) =VCO₂ *Pbar/Prest_(ET)CO₂  (6)

Then at V_(E)rest,Verest=VrestCO₂ *Pbar/Prest_(ET)CO₂  (7)

Substituting 7 into 4, we obtain,PrgCO₂=(Prest_(ET)CO₂ −VrestCO₂ *Pbar/(n*(VrestCO₂*Pbar/Prest_(ET)CO₂))*n/(−1)  (8)

Canceling like terms for numerator and denominator in 8, we obtainPrgCO₂=(Prest_(ET)CO₂ −Prest_(ET)CO₂ /n)*n/(n−1)  (9)

Factoring out Prest_(ET)CO₂ in (9), we obtainPrgCO₂ =Prest_(ET)CO₂*(1−1/n)*n/(n−1)  (10)

Factoring out n in (10), we obtainPrgCO₂ =Prest_(ET)CO₂*((n−1)/n)*n/(n−1)  (11)

Cancelling like terms from (11),PrgCO₂ =Prest_(ET)CO₂  (12)

Therefore, the reserve gas PCO₂ must be equal to the resting end-tidalPCO₂ in order for the condition to be met of end-tidal PCO₂ remainingconstant with increased V_(E).

This provides an additional advantage over Fisher's method, because theresting P_(ET)CO₂ can be obtained more readily than the PvCO₂. Tomaintain P_(ET)CO₂ constant, the PrgCO₂ can be set by simply measuringthe concentration of CO₂ in gas sampled at end-expiration. If this isunknown, the PrgCO₂ can be set equal to the desired PaCO₂ (for example40 mmHg). With higher and higher minute ventilation, the subject's PaCO₂will approach the PrgCO₂, whatever it might have been initially. In thissituation, preferably, the fresh gas flow would also be set equal to therequired alveolar ventilation which would produce the desired arterialPCO₂. This could be empirically determined, or calculated from thealveolar gas equation.

Therefore, from the above it is shown that in order to make PaCO₂independent of minute ventilation (FIG. 6), FGF should be setsubstantially equal to baseline minute ventilation minus anatomical deadspace, and reserve gas PCO₂ should be set substantially equal toarterial PCO₂.

The present invention provides a new equation more fully and accuratelydescribing what is happening than that of Fisher. PvCO₂ in Fisher'sequation has been replaced with PaCO₂. V_(E) in Fisher's equation hasbeen replaced with V_(E)−V_(Dan). Finally, an additional term has beenadded which describes the effect of the alveolar dead space. Thealveolar dead space ventilation has the effect of decreasing the amountof fresh gas and reserve gas by the proportion of total ventilation ofthe alveolar compartment which it occupies.

$V_{A} = \left. {\overset{\_}{1}\frac{V_{D_{a|V}}}{V_{E} - V_{Dan}}\mspace{14mu}}\leftrightarrow{{FGF} + \left( {\left( {V_{E} - V_{Dan}} \right) - {FGF}} \right)}\leftrightarrow{\frac{{- {{Pa}{CO}}_{2}} - {{Prg}{CO}}_{2}}{{{Pa}{CO}}_{2}}} \right.$

FIG. 2 shows the schematic of the standard anaesthetic circle circuit,spontaneous ventilation. When the patient exhales, the inspiratory valve21 closes, the expiratory valve 22 opens and gas flows through thecorrugated tubing making up the expiratory limb of the circuit 23 intothe rebreathing bag 24. When the rebreathing bag 24 is full, the airwaypressure-limiting (APL) valve 25 opens and the balance of expired gasexits through the APL valve 25 into a gas scavenger (not shown). Whenthe patient inhales, the negative pressure in the circuit closes theexpiratory valve 22, opens the inspiratory valve 21, and directs gas toflow through the corrugated tube making up the inspiratory limb of thecircuit 26. Inspiration draws all of the gas from the fresh gas hose 27and makes up the balance of the volume of the breath by drawing gas fromthe rebreathing bag 24. The gas from the rebreathing bag containsexpired gas with CO₂ in it. The CO₂ is extracted as the gas passesthrough the CO₂ absorber 28 and thus is delivered to the patient (P)without CO₂ (but still containing exhaled anaesthetic vapor, if any).

A modification of the circuit as shown in FIG. 2 to allowhyperventilation of patient under anaesthesia is shown in FIG. 3.

The modification comprises:

-   1. A circuit which acts functionally like a standard self inflating    bag (such as made by Laerdal), having:    -   a) a non-rebreathing valve 29, such as valve #560200 made by        Laerdal, that functions during spontaneous breathing as well as        manually assisted breathing;    -   b) an expired gas manifold 30, such as the expiratory deviator        #850500, to collect expired gas and direct it to a gas scavenger        system (not shown) or to the expiratory limb of the anaesthetic        circuit (FIG. 4);    -   c) a self inflating bag 31 whose entrance is guarded by a        one-way valve 32 directing gas into the self inflating bag 31.-   2. A source of fresh gas (i.e., not containing vapor) 33 e.g. oxygen    or oxygen plus nitrous oxide with a flow meter (32).-   3. A manifold 34 with 4 ports:    -   a) port 35 for input of fresh gas 33;    -   b) port 36 for a fresh gas reservoir bag 37;    -   c) port which is attached a one-way inflow valve 38 that opens        when the pressure inside the manifold is 5 cm H₂O less than        atmospheric pressure, such as Livingston Health Care Services        part #9005, (assuring that all of the fresh gas is utilized        before opening);    -   d) a bag of gas 39 whose PCO₂ is equal to approximately to that        of the arterial PCO₂ connected to inflow valve 38        (alternatively, the valve and gas reservoir bag can be replaced        by a demand regulator, such as Lifetronix MS91120012, similar to        that used in SCUBA diving, and a cylinder of compressed gas);    -   e) a port to which a one-way outflow valve 40, such as        Livingston Health Care Services catalog part #9005, that allows        release of gas from the manifold to atmosphere when the pressure        in the manifold is greater than 5 cm H₂O.

The operation method of the anaesthetic circuit is shown as FIG. 4A. Thedistal end of the nonrebreathing valve 29 (Laerdal type) as shown inFIG. 3 is attached to the patient.

The proximal port of the nonrebreathing valve 39 is attached to a 3 wayrespiratory valve 41 which can direct inspiratory gas either from thecircle anaesthetic circuit (FIG. 4B) or from the new circuit (FIG. 4C).The expiratory manifold 30 of the self inflating bag's non rebreathingvalve 29 is attached to the expiratory limb of the anaesthetic circuit23. Regardless of the source of inspired gas, exhalation is directedinto the expiratory limb of the anaesthetic circuit.

To maximize the elimination of anesthetic vapor from the patient's lung,the 3-way respiratory stopcock 41 is turned such that the patientinspiration is from the new circuit (FIG. 4C). Thus inspired gas fromthe very first breath after turning the 3-way valve onward contains novapor, providing the maximum gradient for anaesthetic vapor elimination.

An increased breathing rate will further enhance the elimination ofvapor from the lung. If breathing spontaneously, the patient can bestimulated to increase his minute ventilation by lowering the FGF 42thereby allowing PCO₂ to rise. Using this approach the PCO₂ will riseand plateau independent of the rate of breathing, resulting in aconstant breathing stimulus. All of the ventilation is effective ineliminating vapor.

If the patient is undergoing controlled ventilation, he can also behyperventilated with the self-inflating bag 31. In either case, thepatient's PCO₂ will be determined by the FGF 42. As long as the FGFremains constant, the PCO₂ will remain constant independent of theminute ventilation.

Conventional servo-controlled techniques designed to prevent changes inPCO₂ with hyperpnea are less affected by changes in CO₂ production thanthe circuit; however, they have other limitations. The assumption thatdetected changes in P_(ET)CO₂ are due to a change in PaCO₂ is not alwayswarranted 34. Small changes in ventilatory pattern can “uncouple”P_(ET)CO₂ from PaCO₂, resulting in P_(ET)CO₂ being an inappropriateinput for the control of PaCO₂. For example, a smaller V_(T) decreasesV_(A) (which tends to increase PaCO₂) but will also decrease P_(ET)CO₂,causing a servo-controller to respond with an inappropriate increase ininspired CO₂. Even under ideal conditions, a servo-controlled systemattempting to correct for changes in P_(ET)CO₂ cannot predict the sizeof an impending V_(T) in a spontaneously breathing subjecting and thusdeliver the appropriate CO₂ load. If in an attempt to obtain finecontrol the gain in a servo-control system is set too high, the responsebecomes unstable and may result in oscillation of the control variable31. Conversely, if the gain is set too low, compensation lags 39.Over-damping of the signal results in the response never reaching thetarget. To address these problems, servo-controllers require complexalgorithms 36 and expensive equipment.

When CO₂ production is constant, the circuit has the theoreticaladvantage over servo-controlled systems in that it provides passivecompensation for changes in V. This minimizes changes in V_(A),pre-emptying the need for subsequent compensation. Maintenance of anearly constant V_(A) occurs even during irregular breathing, includingbrief periods when V is less than the FGF. Under this circumstance,excess FGF is stored in the fresh gas reservoir and subsequentlycontributes to V_(A) when ventilation exceeds FGF.

When CO₂ production increases during hyperventilation, as would occurwith increased work of breathing or exercise, our method requiresmodification. To compensate, additional V_(A) can be provided either byincreasing FGF or by lowering the PCO₂ of the reserve gas below thePvCO₂.

As such, a simple circuit that disassociates V_(A) from V has beendescribed. It passively minimizes increases in VA that would normallyaccompany hyperventilation when CO₂ production is constant. It can bemodified to compensate for increases in CO₂ production. The circuit mayform the basis for a simple and inexpensive alternative toservo-controlled systems for research and may have therapeuticapplications.

Referring to FIG. 7, the patient breathes through one port of a Y-piece71. The other 2 arms of the Y-piece contain 1-way valves. Theinspiratory limb of the Y-piece contains a one-way valve, theinspiratory valve 72 which directs gas to flow towards the patient whenthe patient makes an inspiratory effort, and acts as a check valvepreventing flow in the opposite direction during exhalation. The otherlimb of the Y-piece 71, the expiratory limb, contains a one-way valve,the expiratory valve 73, positioned such that it allows gas to exit theY-piece 71 when the patient exhales, and also acts as a check valve toprevent flow towards the patient when the patient inhales. Immediatelydistal to the expiratory limb of the Y-piece is attached large boretubing 74, termed “reservoir tube” that is open at its distal end 75.The reservoir tube is preferably greater then 22 mm in diameter, and itslength is such that the total volume of the tubing is about or greaterthan 3 L when it is being used for an average (70 kg) adult. Largervolumes of reservoir tubing will be required for larger subjects andvice versa. The inspiratory port is connected to a source of fresh gas76, i.e., gas not containing CO₂, flowing into the circuit at a fixedrate and a fresh gas reservoir bag 79 of about 3 L in volume. A bypassconduit 77 connects the expiratory limb and the inspiratory limb. Theopening of the conduit to the expiratory limb is preferably as close aspossible to the expiratory one-way valve. This conduit contains aone-way valve 78 allowing flow from the expiratory to the inspiratorylimb. The conduit's one-way valve 78 allowing flow from the expiratoryto the inspiratory limb. The conduit's one-way valve 78 requires anopening pressure differential across the valve slightly greater thanthat of the inspiratory valve. In this way, during inspiration, freshgas, consisting of fresh gas flow and the contents of the fresh gasreservoir bag, is preferentially drawn from the inspiratory manifold.

When the patient's minute ventilation less anatomical dead space isequal to or less than the FGF, only fresh gas (FG) is breathed. Duringexhalation FG accumulates in the FG reservoir. During inhalation freshgas glowing into the circuit and the contents of the fresh gas reservoirare inhaled. When minute ventilation less anatomical dead space exceedsFGF, on each breath, FG is breathed until the FG reservoir is emptied.Additional inspiratory efforts result in a decrease in pressure on theinspiratory side of the current. When this pressure differential acrossthe valve of the bypass conduit exceed its opening pressure, the one-wayvalve opens and exhaled gas is drawn back from the expired gas reservoirinto the inspiratory limb of the Y-piece and hence to the patient. Thelast gas to be exhaled during the previous breath, termed “alveolar gas”is the first to be drawn back into the inspiratory limb and inhaled(rebreathed) by the subject.

A method of measuring the anatomical dead space can be provided. Thefresh gas flow can be set equal to the minute ventilation less theanatomical dead space ventilation V_(Dan). Fresh gas flow shouldinitially be set approximately equal to the resting minute ventilation.Fresh gas flow can be slowly decreased, for example, 200 mL/min at atime. P_(ET)CO₂, will remain flat initially, and at some point willbegin to rise exponentially. This can be seen in FIG. 8, in which ahuman subject breathes through the circuit while fresh gas flow wasdecreased in steps. This point is defined as the “inflection point”. TheFGF at the inflection point is equal to V_(E)−V_(D)an. It is apparentthat this circuit can therefore be used to measure anatomical dead spaceas the difference between resting ventilation and the inflection point,divided by the respiratory frequency V_(Dan)=(V_(E)−VFGF at inflectionpoint), and anatomical dead space=(V_(E)−FGF at inflection point)/f.Those skilled in the art will recognize that there are other ways to usethis circuit to measure dead space for example measuring the restingV_(E) and P_(ET)CO₂, asking the subject to hyperventilate and thenprogressively decreasing the fresh gas glow until resting P_(ET)CO₂ isreached. Because the rebreathing circuit taught by Fisher works in thesame way, it too can be used to measure anatomical dead space in thisway. Other variations of using these circuits to measure anatomical deadspace will be apparent to those skilled in the art. This method ofmeasuring anatomical dead space can be used with any circuit where freshgas flow limits alveolar ventilation under the conditions where allfresh gas flow is inhaled during breathing.

FIG. 9 shows a portable isocapna circuit. The patient or subjectbreathes (inhales and exhales) through one port of a Y-piece 91. Theisocapnia circuit has another two ports in a form of two limbs of theY-piece 91, and each of them comprises a one-way valve. One of the limbswith an inspiratory valve 92 functions as an inspiration port, while theother limb with an expiratory valve 93 functions as an expiration port.The inspiratory valve 92 directs gas to flow towards the patient whenthe patient makes an inspiratory effort, and acts as a check valvepreventing flow in the opposite direction during exhalation. Theexpiratory valve 93 allows gas to exit the Y-piece 91 when the patientexhales, and also acts as a check valve to prevent flow towards thepatient when the patient inhales. Immediately distal to the expiratorylimb of the Y-piece 91, a large bore tubing termed “alveolar gasreservoir” 94 is attached. The alveolar gas reservoir 94 is contained ina pliable bag of about 3 L in volume. Bag 95, has a proximal end sealedaround a proximal end of the alveolar gas reservoir 94. The expiratorygas reservoir bag 95 further has another tubing called the “exhausttubing” 96 situated at a distal end where the expired gas exits toatmosphere 97. Thus arranged, most of the exhaust tubing 96 is containedin the expiratory gas reservoir bag 95, and which is sealed to thecircumference of the exhaust tubing 96 at its distal end. Preferably,the exhaust tubing 96 has a diameter smaller than that of the alveolargas reservoir 94. In one embodiment, the alveolar gas reservoir 94 isabout 35 mm in diameter, and has a length to provide a total volume ofabout or greater than 0.3 while being applied to an average (70 kg)adult. Distal to the expiratory limb of the Y-piece 91, a large boretubing termed “alveolar gas reservoir” 94 is attached. The alveolar gasreservoir 94 is contained in a pliable bag of about 3 L in volume. Thepliable bag, named “expiratory gas reservoir bag” 95, has a proximal endsealed around a proximal end of the alveolar gas reservoir 94. Theexpiratory gas reservoir bag 95 further has another tubing called the“exhaust tubing” 96 situated at a distal end where the expired gas exitsto atmosphere 97. Thus arranged, most of the exhaust tubing 96 iscontained in the expiratory gas reservoir bag 95, and which is sealed tothe circumference of the exhaust tubing 96 at its distal end.Preferably, the exhaust tubing 96 has a diameter smaller than that ofthe alveolar gas reservoir 94. In one embodiment, the alveolar gasreservoir 94 is about 35 mm in diameter, and has a length to provide atotal volume of about or greater than 0.3 while being applied to anaverage (70 kg) adult.

The inspiratory limb opens into a cylindrical container comprising arigid proximal end plate 98, a collapsible plicate tube 99 extendingdistally from the circumference of the proximate end plate 98, and adistal end rigid plate 110 sealing the distal end of the collapsibleplicate tube 99. When not in use, the collapsible plicate tube 99 iskept open by the gravitation of the distal end rigid plate 110, and/orby the force of a spring 111 attached on the collapsible plicate tube99, and/or by intrinsic recoil of the plicate tubing 99. The inspiratorylimb is also open to the atmosphere by means of a nozzle 112, to which atube 113 is attached. The rigid plate 110 is open to a nozzle 114, towhich another tube 115 is attached. The proximal end plate 98 has aprotuberance 116 pointing at the tube 115 that is aligned with theinternal opening of the distal end plate nozzle 114. The combination ofthe proximal end plate 98, the collapsible plicate tube 99, the distalend rigid plate 110, the spring 111, the inspiratory limb nozzle 112,the tube 113 attached to the nozzle 112, the distal end plate nozzle114, the tube 115 attached to the distal end plate nozzle 114 and theprotuberance 116 are in aggregate as am “atmosphere air aspirator(AAA)”. A bypass conduit 117 is further included in the Y-piece 91 toconnect the expiratory limb and the inspiratory limb. The opening of thebypass conduit 117 is preferably as close as possible to the expiratoryvalve 93. The bypass conduit 117 has a one-way valve 118 allowing flowfrom the expiratory limb to the inspiratory limb only. The one-way valve118 of the bypass conduit 117 requires an opening pressure differentialslightly greater than the pressure difference between the inspiratorylimb pressure and atmospheric pressure that is sufficient to collapsethe plicate tube 99. In this way, during inspiration, atmosphere aircontained in the atmospheric air aspirator and the air beingcontinuously aspirated into the inspiratory limb is preferentially drawnfrom the inspiratory manifold.

Considering the above isocapnia circuit without the spring 111, thenozzle 114 on the distal end plate 114, or the internally directedprotuberance 116, each inspiration drawn initially from the atmosphericair aspirator collapses the plicate tube 99 and approximates the distalend plate 110 to the proximal end plate 18 when the patient begins tobreathe. As long as the plicate tube 99 is partially collapsed, there isa constant sub-atmospheric pressure in the inspiratory limb of theisocapnia circuit. The sub-atmospheric pressure creates a pressuregradient that draws the atmospheric air into the inspiratory limb of theisocapnia circuit through the nozzle 112 and the tube 113. When theminute ventilation of the subject is equal to or less than the intendedflow of atmospheric air into the aspirator, only atmospheric air isbreathed. During exhalation, atmospheric air accumulates in theaspirator. During inhalation, inspired gas consist of the contents ofthe atmospheric air aspirator and the atmospheric air flowing into theinspiratory limb through the nozzle 113. When the minute ventilation ofthe subject exceeds the net flow of the atmospheric air into theisocapnia circuit, air is breathed for each breath until the atmosphericair aspirator is collapsed. Additional inspiratory efforts result in anadditional decrease in gas pressure on the inspiratory side of theisocapnia circuit.

When the pressure differential across the valve 118 of the bypassconduit 117 exceeds its opening pressure, the one-way valve 118 opensand the exhaled gas is drawn back from the expiratory reservoir bag 95into the inspiratory limb of the Y-piece 91 and hence to the patient. Tothe extent that the opening pressure of the valve 118 is close to thepressure generated by the recoil of the atmospheric air aspirator, therewill be little change in the flow of atmospheric air into the isocapniacircuit during inspiration after the atmospheric air aspirator hascollapsed. The last gas to be exhaled during the previous breath, termed“alveolar gas”, is retained in the alveolar gas reservoir 14 and is thefirst gas to be drawn back into the inspiratory limb of the isocapniacircuit and inhaled (rebreathed) by the patient. After several breaths,the rest of the expired gas from the expiratory gas reservoir bag 95contains mixed expired gas. The mixed expired gas from the expiratorygas reservoir bag 95 replace the gas drawn from the alveolar gasreservoir 94 and provides the balance of the inspired volume required tomeet the inspiratory effort of the patient. The greater restriction inthe diameter of the second tube, that is, the exhaust tubing 96, than inthe alveolar gas reservoir 94 results in the gas being drawn into thealveolar gas reservoir 94 being displaced by the collapse of theexpiratory gas reservoir bag 95 in preference to drawing air from theambient atmosphere. The exhaust tubing in the expiratory reservoir bag96 provides a rout for exhaust of expired gas and acts as a reservoirfor that volume of atmospheric air diffusing into the expiratoryreservoir bag through the distal opening, tending to keep suchatmospheric air separate from the mixed expired gas contained in theexpiratory gas reservoir bag 95.

During exhalation and all of inhalation until the collapse of theatmospheric gas aspirator, the flow of atmospheric air into the circuitwill remain constant. However, after the atmospheric air aspiratorcollapses the pressure gradient will increase. The effect of theincrease in total flow will depend on the difference between the openingpressure of the bypass valve 118 and the recoil pressure of theatmospheric air aspirator times the fraction of the respiratory cyclewhen the atmospheric air aspirator is collapsed. If the fraction of therespiratory cycle when the atmospheric air aspirator is collapsed isgreat, as when there is a very great excess minute ventilation above therate of atmospheric air aspiration, the atmospheric air aspirator can bemodified adding a second port for air entry at, for example, the distalend plate nozzle 114. As a result, the total flow from the two portsprovides the desired total flow of air into the circuit under the recoilpressure of the atmospheric air aspirator. When the atmospheric airaspirator collapses on inspiration, the second port 114 is occluded bythe protuberance 116. The remaining port, that is, the nozzle 112,provides a greater resistance to air flow to offset the greater pressuregradient being that gradient required to open the bypass valve 118.

In the above embodiment, it is assumed that the gravitation acting onthe distal plate 110 provides the recoil pressure to open theatmospheric air aspirator. The disadvantage to this configuration isthat the distal end plate 110 must be heavy enough to generate thesub-atmospheric pressure. This may be too heavy to be supported byattachment to a face mask strapped to the face. Furthermore, movementsuch as walking or running or spasmodic inhalation will cause variationsin the pressure inside the atmospheric air aspirator and hence variationin flow of air into the atmospheric air aspirator. In such cases, it isbetter to minimize the mass of the distal end plate 110 and use adifferent type of motive force to provide recoil symbolized by thespring 111.

Preferably the circuit as described above is installed in a case torender it fully portable. The case may include the appropriate number ofcapped ports to allow proper set up and use of the circuit.

Other embodiments of the invention will appear to those skilled in theart from consideration of the specification and practice of theinvention disclosed herein. It is intended that the specification andexamples to be considered as exemplary only, with a true scope andspirit of the invention being indicated by the following claims.

1. An isocapnia circuit, comprising: an exit port, from which gases exitfrom the isocapnia circuit to a patient; a valve, permitting gasesdelivered to the exit port for the patient, but preventing gases frompassing therethrough to the isocapnia circuit; a source of fresh gas,containing a physiologically insignificant amount of CO₂ incommunication with the valve to be delivered to the patient; a fresh gasreservoir, in communication with the source of fresh gas flow forreceiving excess fresh gas not breathed by the patient; and a reservegas supply, in communication with the exit port through the valve andcontaining CO₂ having a PCO₂ approximately equal to PCO₂ in the arterialblood of the subject.
 2. The isocapnia circuit of claim 1, wherein thesource of gas, the fresh gas reservoir and the reserve gas supply aredisposed on a side of the valve remote from the exit port.
 3. Theisocapnia circuit of claim 1, further comprises a pressure relief incommunication with the source of fresh gas and the fresh gas reservoir.4. The isocapnia circuit of claim 1, wherein the reserve gas supplycomprises a demand valve regulator which opens when an additional gas isrequired by the patient, and closes when the additional gas is notrequired.
 5. The isocapnia circuit of claim 1, wherein the valveincludes a non-rebreathing valve through which gas exhaled from thepatient is directed to a gas scavenger.
 6. The isocapnia circuit ofclaim 1, wherein the source of fresh gas is operative to supply thefresh gas in an amount equal to minute ventilation of the subject minusventilation of anatomic dead space of the subject.
 7. The isocapniacircuit of claim 6, further comprising an anesthetic circuit selectivelyin communication with the exit port through the valve.
 8. The isocapniacircuit of claim 7, further comprising a three-way stopcock to switchconnection of the exit port to the isocapnia circuit or the anestheticcircuit.
 9. The isocapnia circuit of claim 1, further comprising aninspiratory gas manifold in communication with the a side of the valveremote to the exit port, the inspiratory gas manifold comprising: afirst port in communication with the source of fresh gas; a second portin communication with the gas reservoir; a third port in communicationwith the reserved gas supply; and a fourth port in communication withatmosphere.
 10. The isocapnia circuit of claim 9, further comprising aself-inflating bag connected having one end in communication with theexit port through the valve and the other end connected to theinspiratory gas manifold.
 11. The isocapnia circuit of claim 10, whereinthe self-inflating bag comprises a one-way valve at the distal end fordirecting gas flowing therein.
 12. The isocapnia circuit of claim 10,wherein the third port includes a one-way valve allowing reserved gasflowing into the inspiratory manifold.
 13. The isocapnia circuit ofclaim 12, wherein the one-way valve of the third port is open whenpressure in the insipratory manifold is about 5 cm H₂O less thanatmospheric pressure.
 14. The isocapnia circuit of claim 10, wherein thefourth port includes a one-way valve allowing gas in the inspiratory gasmanifold released to atmosphere.
 15. The isocapnia circuit of claim 14,wherein the one-way valve of the fourth port opens when pressure in theinspiratory gas manifold is about 5 cm H₂O greater than atmosphericpressure.
 16. A non-rebreathing circuit for maintaining substantiallyconstant isocapnia of a subject, the circuit comprising: anon-rebreathing valve preventing gas exhaled from the subject flowinginto the circuit; a fresh gas source operative to supply a fresh gascontaining physiologically insignificant amount of carbon dioxide to thesubject through the non-rebreathing valve, wherein the fresh gassupplied to the subject is set with a rate equal to a baseline minuteventilation less a ventilation of anatomic dead space of the subject;and a reserved gas source operative to supply a reserved gas having apredetermined partial pressure of carbon dioxide to the subject throughthe non-rebreathing valve.
 17. The non-rebreathing circuit of claim 16,wherein the predetermined partial pressure of carbon dioxide is equal topartial pressure of arterial blood of the subject.
 18. Thenon-rebreathing circuit of claim 17, further comprising a gas reservoiroperative to receive fresh gas in the circuit that is not breathed bythe subject.
 19. The non-rebreathing circuit of claim 16, wherein thereserved gas source is operative to supply the reserved gas only whenminute ventilation of the subject exceeds the flow of the fresh gassupplied.
 20. The non-rebreathing circuit of claim 16, wherein the freshgas comprises oxygen.
 21. The non-rebreathing circuit of claim 16,wherein the fresh gas comprises oxygen and nitrous oxide.
 22. Thenon-rebreathing circuit of claim 16, wherein the reserved gas comprisescarbon dioxide.
 23. The non-rebreathing circuit of claim 16, wherein thenon-rebreathing valve has a proximal end connected to the subject and adistal end in communication with either the fresh gas source or thereserved gas source according on level of minute ventilation of thesubject.